原文：What is the Carbohydrate Insulin Model?
作者：尼古拉斯·诺维茨 博士
日期：2021年5月
快速总结
“碳水化合物-胰岛素模型”提出：当我们食用高升糖碳水化合物（如糖和精制碳水化合物）时，胰岛素激素的变化会导致饥饿感增加和能量消耗减少。长期人体随机对照试验支持碳水化合物-胰岛素模型，而只有动物研究、观察性研究和短期试验反对（此模型）。胰岛素抵抗可能是肥胖流行的根源，碳水化合物-胰岛素模型——通过推荐低碳水化合物饮食——也有助于解决胰岛素抵抗的流行。
“碳水化合物-胰岛素模型”与传统理论有差别，我们需要这个与传统不同的模型，因为卡路里优先理论的“少吃，多运动”的方法是无法解决肥胖流行病。什么导致肥胖？大多数人会告诉你这是一种简单的能量失衡。换句话说，体重增加=摄入的热量− 消耗的热量。
从表面上看，这很有道理。热力学定律必须适用于人类。因此，如果我们“少吃”（卡路里摄入）和“多运动”（卡路里的消耗），我们应该能够减肥，保持健康的体重。这就是CICO（calories in-calories out）理论。
问题是，虽然能量平衡模型在理论上可行，但在实践中却失败了。多年来，社会一直在推行“少吃，多运动”的以卡路里为中心的体重管理方法，但没有成功。事实证明，“少吃，多运动”不足以减缓肥胖症的上升趋势。为了解决肥胖问题，我们需要换一种思路。
如果“少吃，多运动”的建议长期有效，就不会出现肥胖症流行。
定义碳水化合物-胰岛素模型
“碳水化合物-胰岛素模型”（CIM）与以热量为中心的肥胖标准模型形成对比，在此（肥胖标准）模型中，热量摄入和消耗之间的不平衡导致体重增加。在大卫.路德维格博士（Ludwig等人，2018）提出的CIM中，过量摄入高升糖碳水化合物会改变人体内的代谢和激素环境，从而导致暴饮暴食和脂肪增加。
CIM和能量平衡模型都认识到一种关系——基于物理学的能量守恒定律——将能量摄入、能量消耗和体重增加联系起来。然而，在CIM中，因果关系是相反的。CIM提出，从长远来看，肥胖的过程会带来过剩的能量平衡，而不是相反。
换句话说，CIM关注与碳水化合物过量摄入相关的代谢和激素变化，这些变化会改变饥饿驱动力、代谢率和燃料分配，导致长期脂肪增加。CIM做出了几个预测。
饥饿和暴饮暴食
首先，CIM观察到，高升糖碳水化合物通过增加胰岛素比胰高血糖素的比率，在餐后后期，即餐后3-5小时左右，降低循环代谢燃料，可能导致饥饿感增加和暴饮暴食。
一项随机对照喂养试验表明，与低碳水化合物饮食相比，高碳水化合物饮食增加了餐后早期胰岛素，降低了餐后晚期血液中的总能量利用率，包括葡萄糖、脂肪酸和酮体（Shimy等人，2020年）。这在生物学上是有意义的，因为胰岛素可以促进葡萄糖摄取，抑制脂肪分解，并抑制肝脏生成酮体。
这种晚期餐后能量利用率低的现象的实际含义是：高碳水化合物饮食可能会挑战一个人通过长期限制热量来维持减肥的能力。为了支持这种可能性，数据显示，与高脂肪低碳水化合物饮食相比，减肥后，高碳水化合物的体重维持饮食使大脑奖励中心的血流量增加43-51%（Holsen 2021）。
其他数据也表明，即使碳水化合物得到控制，升糖（GI）指数也能预测大脑奖赏中心在晚期餐后激活饥饿感的程度（Lennerz等人，2013年），这意味着在CIM中并非所有碳水化合物的来源都是平等的，因为高GI碳水化合物在更大程度上刺激胰岛素。
总能源消耗
第二，CIM预测，高碳水化合物饮食可以减少能量消耗，以此来捍卫更高的体重设定值。这一预测在“弗雷明翰州立食品研究中”得到了验证，这是一项为期20周的随机对照试验，在该试验中，减轻了体重的个体被随机分配到20%脂肪、60%碳水化合物（低脂）；40%脂肪、40%碳水化合物；或60%脂肪、20%碳水化合物（低碳水化合物）维持体重的饮食中，这些饮食中的蛋白质受到控制，热量被调整以维持体重。研究发现，与低脂组相比，平均120人中，低碳水化合物组每天需要增加278卡路里来维持体重（Ebbeling等人，2018年，Ebbeling等人，2020年）。
燃料分配错误
第三，CIM预测，即使热量得到控制，高胰岛素水平会使燃料分配偏向瘦肌肉，而不是脂肪。这一点已在大鼠（实验）中得到证实: 即使在控制热量摄入和活动以防止体重过度增加的情况下，胰岛素给药也会导致脂肪增加（Torbay等人，1985年）；在高碳水化合物对比低碳水化合物、热量控制饮食的啮齿类动物实验中（Pawlak等人，2004年）。
虽然胰岛素驱动的燃料错误分配的概念很难在人类身上进行实验测试（除了外源性胰岛素治疗的自然实验），但这与其他数据一致，这些数据表明，生活方式干预后9个月和2年，下丘脑胰岛素抵抗与体重恢复有关，以及即使体重指数得到控制的情况下，多余的燃料优先分配到炎症性腹部内脏脂肪。（Kullmann等人，2020年）。
对CIM模型的批评
诚然，有人对CIM提出了批评。例如，“弗雷明翰州食品研究”中使用的双标记水法“理论上……通过生物合成途径的[差异]通量”可能会限制该试验中所用方法的准确性而受到批评（Hall等人，2019年）。然而，这一挑战在一项二次分析中得到了解决，该分析证实，吃低碳水化合物饮食的人每天需要多摄入200-300卡路里才能维持体重（Ebbeling等人，2020年）。
此外，一些研究人员指出，与短期试验中的低脂饮食相比，低碳水化合物饮食似乎不会增加能量消耗。然而，这可能不是一个完全公平的评估，因为生物适应低碳水化合物饮食需要几周时间（Vazquez 1992）。事实上，2021年对29项控制进食研究的Meta分析发现，短于2.5周的研究显示低碳水化合物饮食对总能量消耗有一个小的劣势，而那些超过2.5周的人对低碳水化合物饮食（路德维希2021）表现出更大的优势。因此，重要的是，所有设计用于正确测试CIM的试验应具有足够的持续时间，理想情况下，能量消耗（变化的评估）至少为一个月，身体成分（变化的评估）至少为6个月。
短期研究表明，CICO（卡路里摄入-消耗理论）的效果最好。长期研究表明，低碳水化合物饮食具有优势。生活是一场马拉松。
最近，《科学》杂志发表了一篇观点文章，再次试图攻击CIM。作为一篇观点文章，它没有提供任何新的数据，但试图总结与CIM相反的观点。
这位资深作者在过往对CIM的大部分攻击负有责任，有趣的看到，他是如何构建自己的论点的。他专注于短期试验和小鼠数据的结果，同时试图通过声称“这些结果可能是由于能量消耗的错误计算”来否定路德维格教授进行的长期人类随机对照试验的结果，这一说法之前在同行评议的文献中被驳斥。（Ebbelinget al，2020年）
此外，他解释说，还没有进行长期随机对照试验来反驳CIM，因为这种长期低碳水化合物饮食“由于对健康的潜在危害而引起道德问题”我觉得这很有趣，因为精心搭配的生酮饮食对大多数人来说是安全的，更重要的是，长期随机对照试验和其他长达数年的对照试验已经在食用生酮饮食的人群中安全的进行了。要进一步了解这篇最新科学文章的反驳观点，你可以点击这里。
结束语
这就是说，CIM是一个还未完全经过验证的模型，也不完整。对CIM模型更全面的看法将包括胰岛素峰值和暴饮暴食恶性循环的长期影响，即胰岛素抵抗和代谢功能障碍的发展。
事实上，胰岛素抵抗对全身许多器官的影响，包括肌肉细胞和大脑，可能是肥胖流行的核心。然而，在我们的现代食品环境中，CIM为胰岛素抵抗的发展提供了一个通道，因为高升糖碳水化合物首先促进了导致胰岛素抵抗的恶性循环。
简而言之，CIM为解决肥胖危机的创新方案提供了与众不同的基础。这是不同的（观点）。我们需要不同的方式，因为旧的方式都不起作用。
关于作者的介绍：尼古拉斯·诺维茨博士 （点击后看视频介绍）是营养科学领域的新星。这位25岁的常春藤联盟告别演讲人仅用两年时间就在牛津大学获得了博士学位，目前正在哈佛医学院攻读医学博士学位。他的研究专长是酮症和大脑老化；然而，他发表的科学论文涉及神经科学、心脏病、胃肠道健康、遗传学、骨骼健康、糖尿病等领域。
你可以在Twitter上@nicknorwitz找到尼克。
原文来源：ketodietapp.com
Quick Summary
The carbohydrate insulin model poses that when we eat high-glycemic carbs, such as sugar and refined carbs, changes in the hormone insulin lead to increased hunger and decreased energy expenditure.
Long-term human randomized controlled trials support the carbohydrate insulin model, whereas only animal studies, observational studies, and short-term trials have been used to oppose it.
Insulin resistance may be the root of the obesity epidemic, but the carbohydrate insulin model — by implicating recommending a low-carb diet — can help to address the epidemic of insulin resistance as well.
The Carbohydrate insulin model is something different, and we need difference because a calorie-first “eat less, move more” approach has not worked to address the obesity epidemic.
What causes obesity? Most people will tell you it’s a simple energy imbalance. In other words, weight gain = calories in − calories out.
On the surface, this makes perfect sense. The laws of thermodynamics must apply to humans. Therefore, if we “eat less” (calories in) and “move more” (calories out) we should be able to lose weight and maintain and healthy body weight.
The trouble is, while the energy balance model works in theory, it fails in practice. Society has been pushing the “eat less, move more” calorie-centric approach to weight management for years without success. “Eat less, move more” has proven to be insufficient advice to slow the rising tide of obesity. To solve the obesity problem, we need to think differently.
If “eat less, move more” advice worked long-term, there wouldn’t be an obesity epidemic.
Defining the CIM Model
The “carbohydrate-insulin model” (CIM) contrasts with the calorie focused standard model of obesity, in which an imbalance between calorie intake and output leads to weight gain. In the CIM, proposed by Professor David Ludwig MD PhD ( Ludwig et al, 2018), excessive intake of high glycemic carbohydrates alters metabolic and hormonal environment in the human body to drive overeating and fat gain.
Both the CIM and the energy balance model recognize a relationship — based on the energy conservation low of physics — linking energy intake, energy expenditure and weight gain. However, in the CIM, causality is reversed. The CIM proposes that, over the long term, the process of getting fat leads to a positive energy balance, not the other way around.
In other words, the CIM focuses on the metabolic and hormonal changes associated with excessive carbohydrate consumption that alter hunger drive, metabolic rate, and fuel partitioning, leading to fat gain over the long-term. The CIM makes several predictions.
Hunger and Overeating
First, the CIM observes that high-glycemic carbohydrates, by increasing the insulin-to-glucagon ratio, lowers circulating metabolic fuels in late post-prandial period, around 3 – 5 hours after a meal, potentially leading to increased hunger and overeating.
A randomized controlled feeding trial demonstrated that a high-carbohydrate diet increased early post-prandial insulin and decreased late post-prandial total energy availability in the bloodstream, including glucose, fatty acids, and ketone bodies, as compared to a low-carbohydrate diet ( Shimy et al, 2020). This makes sense biologically as insulin drives glucose uptake, inhibits lipolysis, and inhibits hepatic ketogenesis.
The practical implication of this late-postprandial low energy availability phenomenon is that high-carbohydrate diets could challenge a person’s ability to maintain weight loss through caloric restriction over long-term. In support of this possibility, data show that, after weight loss, high-carbohydrate weight maintenance diets are associated with a 43-51% increased blood flow to the brain’s reward center as compared to higher fat low-carbohydrate diets ( Holsen 2021).
Other data also show that, even when carbohydrates are controlled, glycemic index predicts brain reward center activation late post-prandial feelings of hunger ( Lennerz et al, 2013), implying that not all sources of carbohydrates are equal in the CIM because higher glycemic carbohydrates spike insulin to a greater extent.
Total Energy Expenditure
Second, the CIM predicts that high-carbohydrate diets may decrease energy expenditure as a means to defend a higher weight set point. This prediction was examined in the Framingham State Food Study, a 20-week randomized controlled trial in which individuals who had lost weight were randomly assigned to 20% fat 60% carb (low fat), 40% fat 40% carb, or 60% fat 20% carb (low carb) weight maintenance diets that were controlled for protein and in which calories were adjusted to maintain weight. The study found that, among 120 persons on average, the low carb group required 278 more Calories per day to maintain weight as compared to the low fat group ( Ebbeling et al, 2018, Ebbeling et al, 2020).
Fuel Mispartitioning
Third, the CIM predicts that high insulin levels can bias fuel partitioning towards fat, as opposed to lean mass, even when calories are controlled. This has been demonstrated in rats in which administration of insulin leads to fat gain even when caloric intake and activity are controlled to prevent excessive weight gain ( Torbay et al, 1985) and in rodents with high vs low-carbohydrate, calorie-controlled diets ( Pawlak et al, 2004).
While the concept of insulin-driven fuel mispartitioning is difficult to test experimentally in humans (beyond the natural experiment of exogenous insulin treatment), is consistent with other data showing that hypothalamic insulin resistance is associated with weight regain at nine months and two years after lifestyle intervention, as well as the preferential partitioning of excess fuel into inflammatory abdominal visceral fat, even when body mass index is controlled ( Kullmann et al, 2020).
Criticisms of the CIM Model
There are, admittedly, criticisms of the CIM. For example, the doubly labeled water method used in the Framingham State Food study was criticized on “theoretical possibility that … [differential] fluxes through biosynthetic pathways” could limit the accuracy of the methodology used in that trial ( Hall et al, 2019). However, this challenge was met in a secondary analysis that confirmed that individuals eating a low-carb diet required 200 – 300 more Calories per day to maintain their weight ( Ebbeling et al, 2020).
Additionally, some researchers note that low-carbohydrate diets don’t appear to increase energy expenditure as compared to low-fat diets in short-term trials. However, this might not be an entirely fair assessment, given that biological adaptation to a low carbohydrate diets takes several weeks ( Vazquez 1992). Indeed, a 2021 meta-analysis of 29 controlled feeding studies found that studies shorter than 2.5 weeks duration showed a small disadvantage of low-carbohydrate diets for total energy expenditure, whereas those longer than 2.5 weeks showed a larger advantage for low-carbohydrate diets ( Ludwig 2021). Therefore, it is important that all trials designed to properly test the CIM be of sufficient duration, ideally at least one month for energy expenditure and at least 6 months for body composition.
Short-term studies show CICO works best. Long-term studies show low-carb diets have an advantage. Life is a marathon.
Most recently, an opinion piece was published in Science that tried, again, to debunk the CIM. Being an opinion piece, it didn’t provide any new data but tried to summarize the counterpoints against the CIM.
It was interesting to see how the senior author, who has historically been responsible for most of the attacks on the CIM, structured his argument. He focused on the results of short-term trials and mouse data, while attempting to invalidate the results of long-term human randomized controlled trials performed by Professor Ludwig by claiming that “these results were likely due to a miscalculation of energy expenditure,” a statement that was previously refuted in the peer-reviewed literature. ( Ebbelinget al, 2020)
Additionally, he explains that long-term randomized controlled trials have not been conducted to refute the CIM because such long-term low-carb diets “raise ethical concerns due to potential harm to health.” I find this interesting because well-formulated ketogenic diets are safe for most people and, more importantly, long-term randomized controlled trials and other years-long controlled trials have been conducted in people living on ketogenic diets safely. For further insight into the counterpoints to this most recent Science article, you can click here.
Final Words
That said, the CIM is not a proven model by any means nor is it the entire picture. A more comprehensive view of the CIM model would include the long-term effects of the vicious cycle of insulin spikes and overeating — namely, the development of insulin resistance and metabolic dysfunction.
In truth, the impact of insulin resistance on many organs throughout the body, include muscle cells and the brain, is probably the core of the obesity epidemic. However, in our modern food environment, the CIM provides a gateway to the development of insulin resistance, as high-glycemic carbohydrates establish the vicious cycle that precipitates insulin resistance in the first place.
In a nutshell, the CIM provides a novel foundation for innovating solutions to tackle the obesity crisis. It’s something different. And we need different because business as usual hasn’t worked.
Dr. Nicholas Norwitz is a new shining star in nutrition science. This 25-year-old Ivy League Valedictorian obtained his PhD at Oxford University in just two years and is now pursing his MD at Harvard Medical School. His research expertise is ketosis and brain aging; however, he has published scientific papers on topics ranging from neuroscience to heart disease to gastrointestinal health to genetics to bone health to diabetes.
You can find Nick on Twitter at @nicknorwitz.
原文转载来源：ketodietapp.com
